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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Performed to good scientific standard, but not to GLP.

Data source

Reference
Reference Type:
publication
Title:
Acute pulmonary toxicity of manganese dioxide
Author:
Bergström R
Year:
1977
Bibliographic source:
Scand. J . Work Environ. and Health, 3(1):5-40

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Guinea pigs were exposed to MnO2 dust aerosols for 24 hours in order to assess the following parameters:
-Pulmonary clearance of MnO2
-Number of free lung cells present in the airways after an acute exposure to MnO2
- The phagocytic activity of the alveolar macrophages at different times after MnO2 exposure.
-The effects of an exposure to bacteria (E. cloacae) on the clearance of MnO2, the inflammatory response and the phagocytic activity of alveolar macrophages.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
6-7 animals per cage (55 x 33 x 18 cm)
food and water available ad libitum.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE
- Method of holding animals in test chamber: Animals were put in 4 cages each holding 6-7 animals. The cages were placed in a stainless steel chamber with a volume of 0.67 m³.
- Source and rate of air: MnO2 dust was mixed with sterile filtered air and introduced into the chamber from the top and sucked through the chamber at a flow of 8m³/h.
- System of generating particulates/aerosols: Dust aerosol was generated using a Rag Pe generator
- Method of particle size determination: A ROYCO optical particle counter model 225 was used to measure the size of the particle and their distribution.
- Temperature, humidity, pressure in air chamber: A negative pressure of 5 mm of water was maintained within the chamber during the exposure.

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 87 ±13.4% of particles were ≥ 3.0 µm


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
24 h
Concentrations:
22 ± 9.2 mg MnO2/m³ air
No. of animals per sex per dose:
6-7
Control animals:
yes

Results and discussion

Any other information on results incl. tables

Clearance of MnO2 from the lungs of guinea pigs was rapid; at 7 days post exposure nearly all MnO2 had been cleared. The number of macrophages was significantly decreased immediately after MnO2 exposure; following which a successive increase took place during the following 7 days. The increase in the number of leukocytes followed a wave pattern response with peaks at 1 and 3 days post exposure.

Approx. 50% of macrophages contained phagocytised particles immediately after exposure. This value decreased to 15% 7 days after exposure.

An increased clearance of viable bacteria took place 1 h after exposure to bacteria in animals already exposed to MnO2. This value decreased at 3, 5 and 24 hrs.

Applicant's summary and conclusion

Conclusions:
MnO2 induces pathological reactions in the lung via cellular elements normally present in the lungs.
Executive summary:

Guinea pigs were exposed to MnO2 dust aerosols for 24 hours in order to assess the following parameters:

-Pulmonary clearance of MnO2

-Number of free lung cells present in the airways after an acute exposure to MnO2

- The phagocytic activity of the alveolar macrophages at different times after MnO2 exposure.

-The effects of an exposure to bacteria (E. cloacae) on the clearance of MnO2, the inflammatory response and the phagocytic activity of alveolar macrophages.

Under the conditions of the study clearance of MnO2 from the lungs of guinea pigs was rapid; at 7 days post exposure nearly all MnO2 had been cleared. The number of macrophages was significantly decreased immediately after MnO2 exposure; following which a successive increase took place during the following 7 days. The increase in the number of leukocytes followed a wave pattern response with peaks at 1 and 3 days post exposure. Approximately 50% of macrophages contained phagocytised particles immediately after exposure. This value decreased to 15% 7 days after exposure. An increased clearance of viable bacteria took place 1 hour after exposure to bacteria in animals already exposed to MnO2. This value decreased at 3, 5 and 24 hours.

It can therefore be concluded that MnO2 induces pathological reactions in the lung via cellular elements normally present in the lungs.